We propose to investigate the potential risk of skin and bladder cancer associated with arsenic ingestion through contaminated drinking water in New Hampshire, and to evaluate alternative measures for quantifying individual exposure to toxic metals. Elevated concentrations of arsenic have been detected in drinking water supplies throughout the state of New Hampshire; approximately 5% of the private drinking water supplies contain arsenic levels above the current Safe Drinking Water Standards of 0.05 mg/L and 20% or more contain levels above the proposed standard of 0.002 mg/L. Therefore, we propose to expand our current state-wide case-control study of skin cancer (involving 600 basal cell and 300 squamous cell skin cancer cases and 600 population controls) to include; (1) an assessment of toxic metal concentrations in individual household drinking water supplies and (2) an added case group of 390 bladder cancer patients and 130 additional controls. Drinking water and blood samples drawn on case cases and controls will be used in studies exploring the biologic mechanisms involved in metal toxicity (e.g., genotoxicity in project #2). Analysis of toxic metal concentrations in household drinking water supplies will be performed in collaboration with the ICP-MS Core Facility. Our study will be among the first: (1) to quantify human exposure to arsenic on an individual level, using both biologic and drinking water assessments, and (2) to use these measures to examine the possible cancer risks associated with arsenic-containing drinking water for a geographically defined US population.